Proposed studies and work in progress concern: (1) structural and metabolic relationships among human plasma lipoproteins, (2) lipoprotein abnormalities in disease states (homozygous IIa and nephrotic IIa hyperlipoproteinemias, hypothyroidism, and cerebrotendinous xanthomatosis (CTX)) in which atherogenesis and deposits of sterols in peripheral tissues are increased, and (3) relation of abnormalities in composition and/or structure to physiological functions and metabolism of the lipoproteins. We are comparing normal and abnormal lipoproteins with respect to heterogeneity, morphology, surface structre, apolipoprotein and lipid compositions, and molecular interactions. The work includes further characterization of specific apolipoproteins, including the basis of polymorphism among apolipoproteins AI, D, E, and TPP and the effect of structural variation on lipid binding and other functions of the proteins. We are also investigating the effects of the cholesterol-binding polyene amphotericin B on plasma lipoproteins.